The research proposed for this award will examine functional and structural properties of single cells in the human retina. The three Aims will link the candidate's scientific background and career plans to study the human retina using a combination of adaptive optics (AO) and optical coherence tomography (OCT) which provide high lateral and high axial resolution, respectively (~2.5 ?m in all three dimensions). Aim 1 will use AO-OCT to determine how the microscopic structure of the photoreceptors gives rise to the bands of the outer retina visible in routine clinical images-bands whose anatomical origins are not known precisely. It will test the hypothesis about whether the third band is from multiple reflectors in the interdigitation zone of the RPE or the tips of individual photoreceptors. Aim 1 will also test hypotheses about the contributions of rods and S-cones to the OCT image. Aim 2 will exploit this knowledge to noninvasively measure function in single photoreceptors, and identify a subset of cones, putative S-cones, often thought to be the first cone type to be affected by outer retinal disease. Aim 3 will study the optical properties of the Mller cells which are known to sustain retinal cells, and have been proposed, controversially, to also act as optical fibers for guiding light to the photoreceptors. This Aim will test ideas about Mller cell wave-guiding properties, for the first time, in the living retina. The optical signatures of all of the retinal layers studied in each of the three Aims are seen in clinical OCT images, but their cellular origins are uncertain. The proposed research will thus provide data fundamental to understanding retinal structure and function, and will enrich our understanding of clinical OCT images of retinal disease. During the mentored phase of this Award, the candidate will draw on all phases of his previous vision science experience including adaptive optics and computational analysis of the 3D structure of retinal images, and will expand this experience in significant ways needed for his career plans. This work will be conducted in the laboratory of John S. Werner where AO-OCT instrumentation has been pioneered and conveniently located in the UC Davis Eye Center. One AO-OCT system is available for the candidate's modification and exclusive use. Training will be buttressed by mentoring and didactic courses with advisors, Edward N. Pugh, Jr. and Lawrence S. Morse, who are internationally renowned basic and clinical vision scientists, respectively. Additional didactic components include a 'Fluorescein' course normally taken by residents and fellows in Ophthalmology and a grant-writing course. The training provided through this K99 will set the stage for the candidate's independent career in vision science research.